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Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions

Author

Listed:
  • Pengcheng Yang

    (Hubei University)

  • Lihang Zhu

    (Wuhan University)

  • Shiya Wang

    (Hubei University)

  • Jixing Gong

    (Sun Yat‐Sen University)

  • Jonathan Nimal Selvaraj

    (Hubei University)

  • Lincai Ye

    (National Children’s Medical Center)

  • Hanxiao Chen

    (West China Second University Hospital, Sichuan University)

  • Yaoyao Zhang

    (West China Second University Hospital, Sichuan University)

  • Gongxin Wang

    (Henan SCOPE Research Institute of Electrophysiology Co. Ltd.)

  • Wanjun Song

    (Beijing Geek Gene Technology Co. Ltd.)

  • Zilong Li

    (Hubei University)

  • Lin Cai

    (Hubei University)

  • Hao Zhang

    (National Children’s Medical Center)

  • Donghui Zhang

    (Hubei University
    Huazhong University of Science and Technology)

Abstract

Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFβ inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.

Suggested Citation

  • Pengcheng Yang & Lihang Zhu & Shiya Wang & Jixing Gong & Jonathan Nimal Selvaraj & Lincai Ye & Hanxiao Chen & Yaoyao Zhang & Gongxin Wang & Wanjun Song & Zilong Li & Lin Cai & Hao Zhang & Donghui Zhan, 2024. "Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52221-9
    DOI: 10.1038/s41467-024-52221-9
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    References listed on IDEAS

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